A Regioselective Approach to Trisubstituted 2 (or 6)-Arylaminopyrimidine-5-carbaldehydes and Their Application in the Synthesis of Structurally and Electronically Unique G∧C Base Precursors

An efficient regioselective synthesis of trisubstituted 2(or 6)-arylaminopyrimidine-5-carbaldehydes has
been developed via an SNAr reaction of 2,4,6-trichloropyrimidine-5-carbaldehyde with aniline, methylamine, and alkoxide nucleophiles using a combination of phase-transfer catalysis and more traditional
SNAr reaction conditions. We demonstrate that in a few synthetic steps, highly functionalized fused-bicyclic pyrimidine substrates can be accessed from the trisubstituted 2-arylaminopyrimidine-5-carbaldehydes. Furthermore, these fused-bicyclic compounds are readily derivatized using the Suzuki
cross-coupling reaction to generate electronically and structurally unique G∧C base precursors.

本研究开发了三取代2(或6)-芳胺基嘧啶-5-甲醛（trisubstituted 2(or 6)-arylaminopyrimidine-5-carbaldehydes）的高效区域选择性合成方法：以2,4,6-三氯嘧啶-5-甲醛（2,4,6-trichloropyrimidine-5-carbaldehyde）与苯胺（aniline）、甲胺（methylamine）及烷氧基亲核试剂（alkoxide nucleophiles）为反应底物，结合相转移催化（Phase-Transfer Catalysis）与经典亲核芳香取代反应（SNAr, Nucleophilic Aromatic Substitution）条件，通过SNAr反应实现合成。研究证实，仅需数步合成操作，即可从该类三取代2-芳胺基嘧啶-5-甲醛中间体获得高官能化的稠合双环嘧啶类底物。此外，借助铃木交叉偶联反应（Suzuki Cross-Coupling Reaction），可便捷地对该类稠合双环化合物进行衍生化，从而得到电子特性与结构骨架均独具特色的G∧C碱基前体。